Regulation and Function of Hox gene lin-39 in C elegans

线虫Hox基因lin-39编码一种含有同源结构域的蛋白，类似于 果蝇变形和性梳减少蛋白，LIN-39在线虫中表达 中体区域，包括外阴前体细胞，是正常命运所必需的 这些细胞的测定。在这些外阴前体细胞中，锡-39的消失是协调的 受Wnt和RAS信号通路的调节。我们认为HOX基因LIN-39在 线虫是一种转录调节因子，控制着一组 下游基因，以控制外阴前体细胞的命运。我们建议 实验1)确定Wnt和RAS通路如何调节Lin-39蛋白水平， 2)体外鉴定LIN-39结合部位并测定它们在体内的相关性；3)确定 在体外或体内，磷酸化改变LIN-39的功能，以及4)鉴定和表征 使用基于微阵列的方法，研究由L1N-39调控的靶基因。 已知的HOX蛋白，如LIN-39，在细胞构图中起作用 所有后生动物发育过程中的前后轴和HOX GONE表达缺陷 会导致严重的发育缺陷。尽管HOX蛋白已经在许多 在物种中，只有少数几个靶基因被确定为这些蛋白质的目标基因。因此，很多事情都可以 全面了解这类重要的发育控制基因的功能 通过模型系统中HOX蛋白靶标的特征，包括人类在内的生物体 线虫，其全基因组序列是可用的，功能基因组学方法是可用的。

The C. elegans Hox gene lin-39 encodes a homeodomain-containing protein similar to the Drosophila Deformed and Sex Combs Reduced proteins, lin-39 is expressed in the C. elegans mid-body region, including the vulval precursor cells, and is required for the proper fate determination of these cells. In these vulval precursor cells, the tin-39 gone is coordinately regulated by both Wnt and Ras signaling pathways. We propose that the Hox gene lin-39 in C. elegans functions as a transcriptional regulator that controls the expression of a set of downstream genes in order to control the fates of the vulval precursor cells. We propose experiments to 1) determine how the Wnt and Ras pathways regulate LIN-39 protein levels, 2) identify LIN-39 binding sites in vitro and assay their relevance in vivo, 3) determine whether phosphorylation alters the functions of LIN-39 in vitro or in vivo, and 4) identify and characterize target genes regulated by L1N-39 using a microarray -based approach. Hox proteins such as LIN-39 are known to function in the patterning of cells along the anterior-posterior axis during the development of all metazoans, and defects in Hox gone expression can lead to drastic defects in development. Although Hox proteins have been characterized in many species, only a handful of target genes have been identified for these proteins. Therefore much can be learned about the function of this important class of master developmental control genes in all organisms, including humans, by the characterization of Hox protein targets in the model system C. elegans, for which full genomic sequence is available and functional genomic approaches are available.